Objective: To explore the role of endothelin-1, a potent endothelial-derived vasoconstrictor peptide, in pulmonary hypertension, by measuring its concentration in arterial and venous plasma.
Design: A survey, case series study.
Setting: University-affiliated hospitals and outpatient clinics.
Patients: Twenty-seven patients with pulmonary hypertension: 7 with primary, and 20 with secondary pulmonary hypertension of various causes. The control groups (n = 16) comprised 8 healthy volunteers and 8 patients with coronary artery disease but without evidence of pulmonary hypertension.
Measurements and Main Results: Pulmonary artery pressure was markedly increased (94/43 ±23/13 mm Hg) in the patients with pulmonary hypertension. Venous plasma immunoreactive endothelin-1, measured by a specific radioimmunoassay, was significantly higher in patients with pulmonary hypertension (3.5 ±2.5 pg/mL, P < 0.001) than in normal subjects (1.45 ±0.45 pg/mL), or patients with coronary disease (0.75 ± 0.64 pg/mL). The arterialto-venous ratio of immunoreactive endothelin-1 was significantly greater than unity in primary pulmonary hypertension (2.21 ± 0.72, P = 0.01), whereas the patients with secondary pulmonary hypertension had a mean ratio not different from 1 (0.97 ± 0.42). In contrast, the mean arterial-to-venous ratios were significantly less than unity in both control groups (0.59 ± 0.35, and 0.54 ± 0.64; P < 0.02, for normal subjects and coronary disease patients, respectively), indicating a possible clearance of endothelin-1 across the healthy lung.
Conclusions: Patients with pulmonary hypertension have substantial alterations in plasma immunoreactive endothelin-1, which may reflect changes in net release or clearance of endothelin-1 by the lung. In patients with primary pulmonary hypertension, the high levels in arterial compared with venous plasma suggest pulmonary production of endothelin-1, which may contribute to elevated pulmonary vascular resistance.